Targeted Interleukin-10 Nanotherapeutics Developed with a Microfluidic Chip Enhance Resolution of Inflammation in Advanced Atherosclerosis.

Item request has been placed! ×
Item request cannot be made. ×
loading   Processing Request
Read More Add to Saved list
  • Additional Information
    • Source:
      Publisher: American Chemical Society Country of Publication: United States NLM ID: 101313589 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1936-086X (Electronic) Linking ISSN: 19360851 NLM ISO Abbreviation: ACS Nano Subsets: MEDLINE
    • Publication Information:
      Original Publication: Washington D.C. : American Chemical Society
    • Subject Terms:
      Microfluidics* ; Nanoparticles*; Atherosclerosis/*therapy ; Interleukin-10/*therapeutic use; Animals ; Atherosclerosis/immunology ; Inflammation ; Mice ; Mice, Knockout ; Plaque, Atherosclerotic
    • Abstract:
      Inflammation is an essential protective biological response involving a coordinated cascade of signals between cytokines and immune signaling molecules that facilitate return to tissue homeostasis after acute injury or infection. However, inflammation is not effectively resolved in chronic inflammatory diseases such as atherosclerosis and can lead to tissue damage and exacerbation of the underlying condition. Therapeutics that dampen inflammation and enhance resolution are currently of considerable interest, in particular those that temper inflammation with minimal host collateral damage. Here we present the development and efficacy investigations of controlled-release polymeric nanoparticles incorporating the anti-inflammatory cytokine interleukin 10 (IL-10) for targeted delivery to atherosclerotic plaques. Nanoparticles were nanoengineered via self-assembly of biodegradable polyester polymers by nanoprecipitation using a rapid micromixer chip capable of producing nanoparticles with retained IL-10 bioactivity post-exposure to organic solvent. A systematic combinatorial approach was taken to screen nanoparticles, resulting in an optimal bioactive formulation from in vitro and ex vivo studies. The most potent nanoparticle termed Col-IV IL-10 NP22 significantly tempered acute inflammation in a self-limited peritonitis model and was shown to be more potent than native IL-10. Furthermore, the Col-IV IL-10 nanoparticles prevented vulnerable plaque formation by increasing fibrous cap thickness and decreasing necrotic cores in advanced lesions of high fat-fed LDLr(-/-) mice. These results demonstrate the efficacy and pro-resolving potential of this engineered nanoparticle for controlled delivery of the potent IL-10 cytokine for the treatment of atherosclerosis.
      Competing Interests: The authors declare the following competing financial interest(s): O.C.F. has financial interests in BIND Therapeutics, Selecta Biosciences, Tarveda Therapeutics and Placon Therapeutics, which are developing nanoparticle technologies for medical applications. These companies did not support the aforementioned research and currently have no rights to any technology or intellectual property developed as part of this research. All other authors declare no conflicts.
    • References:
      Arterioscler Thromb Vasc Biol. 2005 Nov;25(11):2255-64. (PMID: 16141399)
      Nat Rev Immunol. 2010 Jan;10(1):36-46. (PMID: 19960040)
      Int J Pharm. 2011 Aug 30;415(1-2):34-52. (PMID: 21640806)
      J Pathol. 2013 Sep;231(1):8-20. (PMID: 23794437)
      Nat Rev Drug Discov. 2014 Sep;13(9):655-72. (PMID: 25103255)
      Circulation. 2007 Oct 16;116(16):1832-44. (PMID: 17938300)
      Circ Res. 2014 Jan 31;114(3):421-33. (PMID: 24297735)
      Proc Natl Acad Sci U S A. 2013 Nov 5;110(45):18232-7. (PMID: 24108355)
      Acc Chem Res. 2011 Oct 18;44(10):1123-34. (PMID: 21692448)
      Physiol Rev. 2006 Apr;86(2):515-81. (PMID: 16601268)
      Cell Immunol. 2011;266(2):165-71. (PMID: 20979991)
      Nature. 2007 Jun 14;447(7146):869-74. (PMID: 17568749)
      Cell. 2015 Feb 26;160(5):816-27. (PMID: 25723161)
      Nat Rev Immunol. 2009 Jan;9(1):62-70. (PMID: 19104500)
      Eur J Immunol. 2011 May;41(5):1203-17. (PMID: 21523780)
      FASEB J. 2008 Oct;22(10):3595-606. (PMID: 18559988)
      Proc Natl Acad Sci U S A. 2013 Apr 16;110(16):6506-11. (PMID: 23533277)
      Blood. 2013 Oct 10;122(15):2714-22. (PMID: 23974197)
      Sci Transl Med. 2014 Jun 4;6(239):239sr1. (PMID: 24898749)
      Crit Rev Immunol. 2012;32(1):23-63. (PMID: 22428854)
      Annu Rev Immunol. 2001;19:683-765. (PMID: 11244051)
      Nat Rev Cancer. 2003 Jun;3(6):422-33. (PMID: 12778132)
      ACS Nano. 2011 Nov 22;5(11):8454-8. (PMID: 21992178)
      Sci Transl Med. 2015 Feb 18;7(275):275ra20. (PMID: 25695999)
      Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19347-52. (PMID: 22087004)
      Eur J Immunol. 2001 Jul;31(7):1981-8. (PMID: 11449350)
      J Am Coll Cardiol. 2015 Jun 23;65(24):2638-51. (PMID: 26088304)
      Circ Res. 2014 Jun 6;114(12):1867-79. (PMID: 24902971)
      FASEB J. 2007 Feb;21(2):325-32. (PMID: 17267386)
      Am J Med. 2011 Aug;124(8):724-30. (PMID: 21787901)
      ACS Nano. 2013 Dec 23;7(12):10671-80. (PMID: 24215426)
      Arterioscler Thromb Vasc Biol. 1999 Dec;19(12):2847-53. (PMID: 10591660)
      Atherosclerosis. 2006 Sep;188(1):19-27. (PMID: 16300768)
      Nat Rev Drug Discov. 2011 Oct 21;10(11):835-52. (PMID: 22015921)
      Int J Pharm. 2008 Jun 5;357(1-2):235-43. (PMID: 18384984)
      Prog Cardiovasc Dis. 2002 Mar-Apr;44(5):349-56. (PMID: 12024333)
      Semin Immunol. 2015 May;27(3):184-93. (PMID: 25865626)
      Gut. 2002 Feb;50(2):191-5. (PMID: 11788558)
      FEBS J. 2012 Oct;279(20):3791-9. (PMID: 22909341)
      ACS Nano. 2014 Jun 24;8(6):6056-65. (PMID: 24824296)
      Nano Lett. 2014 Nov 12;14(11):6449-55. (PMID: 25333768)
      Int J Nanomedicine. 2014 Sep 03;9:4211-22. (PMID: 25214785)
      Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):2213-8. (PMID: 20133865)
      Proc Natl Acad Sci U S A. 2008 Feb 19;105(7):2586-91. (PMID: 18272481)
      Drug Dev Ind Pharm. 1998 Dec;24(12):1113-28. (PMID: 9876569)
      J Immunol. 2005 Sep 1;175(5):3354-9. (PMID: 16116228)
      Immunity. 2014 Mar 20;40(3):315-27. (PMID: 24656045)
      J Immunol. 2011 May 15;186(10):5543-7. (PMID: 21460209)
      Mol Pharm. 2013 Jan 7;10(1):175-86. (PMID: 23176185)
      Science. 2013 Jan 11;339(6116):166-72. (PMID: 23307734)
      Nat Rev Cardiol. 2015 Apr;12(4):199-211. (PMID: 25666404)
      Nature. 1976 Oct 28;263(5580):797-800. (PMID: 995197)
      Cell. 2011 Apr 29;145(3):341-55. (PMID: 21529710)
      Arterioscler Thromb Vasc Biol. 2008 Aug;28(8):1421-8. (PMID: 18451332)
      Sci Transl Med. 2015 Feb 18;7(275):275fs7. (PMID: 25695998)
      J Immunol. 2005 Apr 1;174(7):4345-55. (PMID: 15778399)
      Chem Soc Rev. 2012 Apr 7;41(7):2971-3010. (PMID: 22388185)
      J Biol Chem. 2004 Dec 3;279(49):51697-703. (PMID: 15465816)
      Adv Drug Deliv Rev. 2014 Feb;66:2-25. (PMID: 24270007)
      Atherosclerosis. 2015 Aug;241(2):772-82. (PMID: 26058741)
      J Immunol. 2000 Sep 1;165(5):2783-9. (PMID: 10946310)
    • Grant Information:
      HHSN268201000045C United States HL NHLBI NIH HHS; R00 HL119587 United States HL NHLBI NIH HHS; U54 CA151884 United States CA NCI NIH HHS; P30 NS072030 United States NS NINDS NIH HHS; R01 HL107497 United States HL NHLBI NIH HHS; R01 EB015419 United States EB NIBIB NIH HHS; R01 HL132412 United States HL NHLBI NIH HHS; R01 HL127464 United States HL NHLBI NIH HHS; R01 HL075662 United States HL NHLBI NIH HHS; K99 HL119587 United States HL NHLBI NIH HHS
    • Contributed Indexing:
      Keywords: IL-10; atherosclerosis; inflammation; microfluidics; nanomedicine; polymeric nanoparticles
    • Accession Number:
      130068-27-8 (Interleukin-10)
    • Publication Date:
      Date Created: 20160422 Date Completed: 20180727 Latest Revision: 20220409
    • Publication Date:
      20240829
    • Accession Number:
      PMC5199136
    • Accession Number:
      10.1021/acsnano.6b01114
    • Accession Number:
      27100066